Analysis of Heat Exposure During Pregnancy and Severe Maternal Morbidity

Key Points Question Is maternal environmental heat exposure associated with increased risk of severe maternal morbidity? Findings In this cohort study with 403 602 pregnancies from 2008 to 2018 in Southern California, statistically significant associations were observed between both long- and short-term maternal heat exposure during pregnancy and increased risks of severe maternal morbidity. Meaning Maternal heat exposure during pregnancy is a potential environmental risk factor for severe maternal morbidity.


Introduction
Severe maternal morbidity (SMM) is considered a near-miss for maternal mortality, referring to severe and unexpected conditions during labor and delivery. 1,24][5][6][7] The rate of SMM in 2014 was almost 3 times that of 20 years ago. 1 Some explanations have been proposed, such as improvement in case identification and changes in maternal characteristics (eg, more mothers with an early or advanced age or obesity), 3,[8][9][10] but those proposed factors cannot fully explain the upward trend of SMM. 1 It is thus imperative to identify more preventable risk factors for SMM, 11 such as climate-sensitive exposure.
4][15] A recent study identified geographic hotspots with elevated risks of SMM in South Carolina (ie, high-risk SMM clusters). 16By differentiating the characteristics between individuals with SMM living in high-risk clusters vs nonclusters, the authors found that individuals exposed to extreme heat during pregnancy were more likely to live in high-risk SMM clusters. 16So far, extreme heat has been associated with many adverse obstetric outcomes, including preterm birth, premature rupture of membranes, low birth weight, and stillbirth, 13,[17][18][19] while little evidence is available regarding individual-level SMM risk.
Identifying modifiable environmental factors, such as extreme heat, can be critical for minimizing SMM risks.
In recent years, cardiovascular conditions have become a leading cause of pregnancy-related deaths. 3,8,11,20,213][24] Given the susceptibility of pregnant women, it would also be meaningful to investigate the underlying relationships between heat and maternal cardiovascular conditions with SMM, which may help to explain potential associations between heat and SMM and guide a more targeted intervention for minimizing heat-related SMM risks.In addition, since extreme heat may be increasingly associated with adverse maternal health outcomes in the changing climate, identifying effect modifiers such as maternal characteristics or other environmental factors (eg, residential green space) would provide important information for designing and implementing interventions for SMM.
We conducted a retrospective cohort study to estimate associations between long-and shortterm maternal heat exposure and SMM.Furthermore, we examined potential effect modification by maternal characteristics and green space exposure.

Study Population
pregnancy from KPSC's electronic health records. 18,25,26The gestational age of pregnancies in the KPSC cohort ranged from 20 to 47 weeks and was estimated based on early pregnancy ultrasonography examinations or self-reported last menstrual period (eMethods in Supplement 1).
Race and ethnicity data were self-reported and recorded in the social history of electronic health records.The data were reported to account for differences in risk of SMM and to assess potential differences in susceptibility to heat exposure.The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline, and was approved by the institutional review board of the KPSC with a waiver for informed consent, as the research was considered minimal risk for participants.

Outcome Ascertainment
We identified SMM cases during delivery hospitalization based on the US Centers for Disease Control and Prevention SMM index using corresponding 9th and 10th revisions of the International Classification of Diseases (ICD) codes 27,28 (eMethods in Supplement 1).The SMM index included 21 indicators shown in eTable 1 in Supplement 1, and a mother with any of those indicators was diagnosed with SMM (denoted as SMM 21 given 21 indicators included).9][30] Following prior studies, we selected SMM 20 , SMM measured without blood transfusion, as the primary outcome in our study.For the secondary outcome, we selected cardiovascular conditions in SMM, denoted as SMM cardio .To define this subcategory, we combined cardiovascular conditions with other conditions of similar pathoetiology (eg, eclampsia or cerebrovascular disorders), for a total of 9 conditions (eTable 1 in Supplement 1).

Heat Exposure Assessment During Pregnancy
We obtained daily maximum temperature data from 2007 to 2018 in Southern California at a 4 km × 4 km resolution from the gridMET data set. 31We assigned daily maximum temperature values during pregnancy to each individual based on their geocoded home addresses accounting for residential mobility.We excluded pregnancies if they had less than 75% temperature data available during pregnancy (n = 22 120 [5.2%]) due to missing residential information.We compared the characteristics of included vs excluded pregnancies (eTable 2 and eResults in Supplement 1).For pregnancies with 25% or less missing data (n = 12 906 [3.0%]), we assigned the temperature data of the following home address to the preceding period with missing data.
For long-term heat exposure, we measured the proportions of heat days during pregnancy under 3 definitions of heat days (ie, moderate, high, and extreme).Following recent studies in Southern California focusing on heat exposure, 18,19,32 we defined the moderate, high, and extreme heat days (denoted as HD_P75, HD_P90, and HD_P95, respectively) as daily maximum temperatures exceeding the 75th, 90th, and 95th percentiles of the time series data from May through September 2007 to 2018 in Southern California, respectively.After checking the distribution of the proportions of heat days, we found that the data were highly and positively skewed.The proportions of moderate, high, and extreme heat days during pregnancy had a skewness of 1.62, 4.73, and 8.43, respectively.Therefore, we dichotomized the exposure variable as low (less than 80th percentile of the proportions) vs high (80th percentile or higher of the proportions) levels.

Green Space Exposure Assessment
We estimated green space exposure based on street view images within a 500 m radius surrounding the residential address at delivery 33,34 and obtained data from a validated machine-learning model developed in our prior study. 35,36In brief, we collected street view images in Southern California from Microsoft Bing Maps Application Programming Interface for each street sampling location with an interval of 200 m.We then estimated the exposure to total green space and 3 different subtypes of green space (ie, trees, low-lying vegetation, and grass) by averaging the proportions of corresponding greenery pixels in all street view images within the 500 m buffer. 35,36

Statistical Analysis
Summary statistics were calculated for the characteristics of the study population and exposure variables.We applied the discrete-time logistic regression to examine associations between longand short-term heat exposure and SMM.8][39] In this study, we estimated associations based on the proportional hazards assumption by using the discrete-time method in our main analysis and compared the results with that of the Cox proportional hazards model in the sensitivity analysis.We examined associations with long-term heat exposure during the entire pregnancy and by trimester.We examined associations with short-term heatwave exposure during the final gestational week for mothers with deliveries in the hottest period of the year (May to September).Given that the results of short-term heat exposure and SMM cardio may be imprecise due to limited SMM cardio cases in the study period (n = 289), we estimated associations with short-term heat exposure for only the primary outcome, SMM 20 .We selected potential covariates a priori according to existing literature (eMethods in Supplement 1), 16,28 including maternal age, race and ethnicity, education level, income level, year of delivery, and season of conception.The results were represented by odds ratios (ORs) with corresponding 95% CIs.
We examined effect modification on the multiplicative scale of entire-pregnancy associations for the primary outcome by maternal age, race and ethnicity, education level, income level, smoking, season of conception, and green space exposure using interaction terms. 39For the season of conception, we examined associations in the cold season (November to April) vs the warm season (May to October).For green space exposure, we examined effect modification by different levels (high [Ն50th] vs low [<50th]) of exposure to total green space, trees, low-lying vegetation, and grass in separate models.
In the sensitivity analysis, we examined associations with SMM 21 and explored some prevalent SMM subconditions, including blood transfusion (SMM blood_transf ), disseminated intervascular coagulation (SMM DIC ), and sepsis (SMM sepsis ).More analyses conducted to check the robustness of our results are described in eMethods in Supplement 1.
A 2-sided P value <.05 was considered statistically significant.All analyses were performed with SAS software version 9.4 (SAS Institute).Adjustment for multiple comparisons was not made for the secondary outcome or any outcome in the sensitivity analysis, and those results should be interpreted as exploratory.

Long-Term Heat Exposure and Risk of SMM
The adjusted ORs and corresponding CIs of SMM 20 and SMM cardio associated with high exposure to heat days (Ն80th percentile of proportions) are shown in Table 4. Significantly increased risk of SMM 20 and SMM cardio were mainly associated with heat exposure during the entire pregnancy and the third trimester.The magnitude of associations was higher for more severe heat exposure.High exposure to HD_P95 during pregnancy was associated with a 27% increase in SMM 20 risk (95% CI,

Short-Term Heatwave Exposure and Risk of SMM
The Figure shows associations between exposure to heatwaves during the last gestational week and SMM 20 .All associations were significant under different heatwave definitions.The magnitude of associations generally increased from the least severe (HWD1: daily maximum temperature >75th percentile lasting for Ն2 days; OR, 1.32; 95% CI, 1.17-1.48;P < .001) to the most severe heatwave exposure (HWD9: daily maximum temperature >95th percentile lasting for Ն4 days; OR, 2.39; 95% CI, 1.62-3.54;P < .001).

Effect Modification by Maternal Characteristics and Green Space Exposure
We observed significant interactions between long-term heat exposure and 2 maternal characteristics, that is, education level and season of conception (eTable 3 in Supplement 1).We observed significantly higher associations between heat exposure and SMM 20 among mothers who did not attend college or whose pregnancies began in the cold season than those with a higher academic degree or starting pregnancies in the warm season, respectively.Although the interaction of other characteristics was not statistically significant, we observed consistently higher associations among mothers younger than 25 years or 35 years and older, from a Hispanic racial or ethnic background, with a lower income level, who smoked, or who had less exposure to trees or grass (eTables 3 and 4 in Supplement 1).

Sensitivity Analyses
We observed associations of SMM 21 with only short-term heat exposure (eTables 5 and 6 in Supplement 1).Increased risks of SMM sepsis were consistently associated with long-and short-term heat exposure.We observed negative associations of SMM blood_transf with long-term heat exposure.
The results of other sensitivity analyses were comparable to those of our main analyses (eResults and eTables 7 and 8 in Supplement 1).

Discussion
In this large retrospective cohort study, long-and short-term maternal exposure to environmental heat was significantly associated with higher SMM risks during delivery hospitalization.We also identified effect modification by the education level and season of conception.
1][42][43] To provide new insights for SMM prevention, we focused on environmental risk factors that have not been examined previously.We observed that experiencing more heat days during pregnancy was associated with increased risks of SMM, where risks increased as heat exposure became more extreme.Associations observed in the third trimester indicated that late pregnancy might be a more sensitive window to environmental heat.We noticed that women who started pregnancy in the cold season were more vulnerable to heat exposure, likely because they would experience their late pregnancy in the hottest period in Southern California (May-September).By comparison, those who started pregnancy in the warm season may experience fewer heat days in their third trimester.Associations with heatwaves observed at the end of pregnancy also support the heat impact in late pregnancy.
Following existing research on SMM, 16,[28][29][30] we estimated associations with SMM 20 (SMM measured without blood transfusion) and with SMM 21 (SMM measured with all indicators).We found that associations with SMM 21 were much weaker compared with those of SMM 20 , especially for associations with long-term heat exposure.We further explored associations with SMM blood_transf and found negative associations with long-term heat exposure.Preeclampsia is one of the most frequent causes of uterine atony and postpartum hemorrhage, 44,45 which can result in blood transfusion during delivery hospitalization. 46A previous study reported that cold ambient temperature was positively associated with, while hot temperature was negatively associated with, the incidence of preeclampsia, 47 which might be a potential explanation for negative associations between heat exposure and SMM blood_transf .Physiologic evidence also suggests a positive association between a cold pressor stimulus as well as skin cooling and preeclampsia. 48,49Without information about the number of blood transfusion units, the diagnosis of SMM blood_transf may not accurately reflect the severity of maternal conditions, which can lead to bias in our results.Additional physiologic, clinical, and observational experience is needed to elucidate the associations between environmental heat, blood transfusion during delivery, and circumstances in pregnancy indicating the need for blood.
1][52] We observed a higher magnitude of associations with long-term heat exposure and SMM cardio compared to associations with SMM 20 , although results for SMM cardio were less precise with wider 95% CIs due to fewer cases.It suggests that the cardiovascular subconditions of SMM may play a critical role in associations between heat exposure and SMM.[53][54][55][56] We also looked at other prevalent SMM subconditions and observed significant associations for SMM sepsis .One possible explanation was that the hypovolemia resulting from heat exposure may promote localized infection to sepsis. 57and may have limited knowledge or awareness to protect themselves against extreme heat.[60] Racial and ethnic disparities in SMM prevalence are known to persist. 61,62Even though we did not observe a statistically significant effect modification between heat and race and ethnicity in associations between heat exposure and risk of SMM, we observed a higher magnitude of associations in Hispanic mothers.4][65] Due to a relatively small sample size of the African American pregnant population in our study, results for this group were less precise compared with others.To interpret racial and ethnic heterogeneity, researchers have called for considering race as a socially defined construct. 61,66We observed higher proportions of mothers with a lower education or income level in our cohort for African American and Hispanic populations compared with Asian or non-Hispanic White mothers.Moreover, we found significantly higher associations between heat exposure and risk of SMM among mothers with a lower education level.Our observation of worse health outcomes among women with lower socioeconomic status may reflect the broader impacts of the persistent and pervasive social injustice issues, including higher adverse exposure levels, more cumulative stressors, more underlying health conditions, and lack of resources and opportunities among these vulnerable populations. 67een space is a potential heat mitigation strategy.Mothers living with more trees or grass around their residences tended to have lower heat-related SMM risks, even though the effect modification was not statistically significant.9][70][71] Our results may have potential implications for increasing adaptability to extreme heat.

JAMA Network Open | Environmental Health
To our knowledge, this is the first study providing evidence of associations between heat exposure during pregnancy and individual-level SMM risk.We also explored heat-related risks of cardiovascular and other subconditions of SMM.Other strengths included the large and diverse pregnancy cohort, the high-quality and rich clinical databases with detailed information on residential mobility during pregnancy, and an extensive analysis of effect modification by maternal characteristics as well as green space exposure.

Limitations
Some limitations should be acknowledged.First, we examined only ambient temperature and did not consider individual-level time-activity patterns (eg, time indoors or in the workplace) or adaptation behaviors (eg, self-dousing or using air conditioning or fans) due to data unavailability, which may have led to exposure misclassification and biased estimated associations in either direction.Second, we only considered SMM during delivery hospitalization and did not have data during postpartum hospitalizations, which may have led to an underestimation of the overall SMM cases and biased results in either direction. 5Third, by using gridded surface air temperature data at a 4-km resolution, we were unable to capture the microscale influences of urban heat islands, which may deserve further investigation. 18Fourth, the participants in our study were from a single health care organization in Southern California, which limits the generalizability of our findings.Further studies in other regions with various climates and diverse populations are warranted.Residual confounding resulting from other factors that were not controlled may also exist in this study.

JAMA Network Open | Environmental Health
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Table 2 .
Descriptive Statistics of Heat and Green Space Exposures During the Entire Pregnancy for the Study Population Based on SMM Status, 2008 to 2018

Table 3 .
Characteristics of Heatwave Definitions and Numbers of Pregnancies Exposed to Heatwaves From May Through September 2008 to 2018The total number of SMM 20 cases from May through September 2008 to 2018 was 1580.We observed a higher magnitude of associations for SMM cardio than SMM 20 .The highest risk of SMM cardio was associated with high exposure to HD_P95 during the third trimester (OR, 1.51; 95% CI, 1.22-1.87;P < .001).

Table 4 .
Adjusted Odds Ratios (ORs) With 95% CIs of SMM 20 and SMM cardio Associated With High Exposure to Heat Days (≥80th Percentile of Proportions) Figure.Adjusted Odds Ratios (ORs) With 95% CIs of Severe Maternal Morbidity Associated With Exposure to Heatwaves Under Different Definitions During the Last Gestational Week a Models adjusted for maternal age, race and ethnicity, education level, income level, year of delivery, and season of conception.
Analysis of Heat Exposure During Pregnancy and Severe Maternal Morbidity Mothers younger than 25 years or 35 years and older might be more susceptible to heat-related SMM risks.Higher risks of obstetric problems associated with adolescent and advanced-age pregnancies have been well recognized.Adolescent mothers are more likely to be in unfavorable social or physical conditions Downloaded From: https://jamanetwork.com/ on 09/23/2023